{"id":"db79f13475f0","type":"article","url":"https://hartvaat.nl/2026/09/01/metformin-verlaagt-risico-op-buikaorta-aneurysma-mr-en-cohortanalyse/","title":"Metformin verlaagt risico op buikaorta-aneurysma — MR- en cohortanalyse","title_en":"Evidence of a Protective Effect of Metformin on Abdominal Aortic Aneurysm Risk: Insights From an Observational Study and Mendelian Randomisation Analysis Using Putative Metformin Targets.","category":"preventie","category_label":"Preventie","professions":["cardioloog","internist"],"tags":[],"journal":"Annals of human genetics","doi":"10.1111/ahg.70049","source_url":"https://doi.org/10.1111/ahg.70049","authors":["Katie Louise Saxby","Svetlana Stoma","Frank Dudbridge","Nilesh J Samani","Matthew J Bown","Christopher P Nelson"],"significance":5,"published":"2026-08-20","source_date":"2026-09-01","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ezetimib/","https://hartvaat.nl/kennis/lipiden/lpa-meten-wanneer-waarom/"],"congress":"","summary_en":"Combining a large UK Biobank cohort study with a two-sample Mendelian randomisation analysis, researchers investigated whether metformin use causally reduces the risk of abdominal aortic aneurysm (AAA). Observational data showed a strong protective association (OR 0.49), which was corroborated by genetic analysis indicating a 43% risk reduction per standard deviation decrease in HbA1c via metformin targets (OR 0.57; p = 0.010). While the findings suggest a potential causal link, they remain observational and genetically inferred. Dedicated clinical trials are required to evaluate whether metformin can effectively slow AAA progression or prevent rupture in patients.","created":"2026-08-13T01:17:51Z","updated":"2026-08-13T01:17:51Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Een combinatie van een groot cohortonderzoek in de UK Biobank en een Mendeliaanse randomisatieanalyse suggereert dat metformin het risico op buikaorta-aneurysma (AAA) aanzienlijk verlaagt. De observatiestudie toonde een odds ratio (OR) van 0,49, terwijl de genetische analyse een risicodaling van 43% bevestigde (OR 0,57; p = 0,010). Hoewel deze bevindingen een causaal verband ondersteunen, blijft het bij observationele en genetische data. Klinische trials zijn nodig om te bepalen of metformin daadwerkelijk kan worden ingezet om de groei of ruptuur van AAA te remmen.","abstract_original":"AIMS: There is no proven treatment to prevent the growth or rupture of abdominal aortic aneurysm (AAA). As an aneurysm enlarges over time, the risk of fatal aortic rupture increases. Metformin, a drug usually prescribed to treat Type 2 diabetes, has previously been associated with reduced AAA risk in observational studies. Our aim was to assess whether there was a causal association between metformin treatment and AAA using Mendelian randomisation (MR). METHODS: Logistic regression analysis was conducted in UK Biobank with 2972 AAA cases and 89,160 propensity-matched controls. In addition, two-sample MR analysis was performed, using a genetic proxy for metformin consisting of variants associated with both gene expression of seven metformin drug targets and decreased glycated haemoglobin (HbA1c) levels. Effect sizes for HbA1c were obtained from within UK Biobank, and for AAA risk from AAAgen, a multi-ancestry meta-GWAS analysis of 39,221 cases and 1,086,107 controls. RESULTS: We found evidence of a protective association between self-reported metformin treatment and reduced AAA risk in the observational analysis, OR 0.49 (95% CI: 0.41-0.59, p = 1.5 × 10-14). MR results support this finding, with an estimated decrease in AAA risk of 43%, OR = 0.57 (95% CI: 0.38-0.88, p = 0.010) per one standard deviation (sd) decrease in HbA1c via metformin gene targets, equivalent to the effect of a prescribed dose of metformin. This effect is specific to metformin target genes and was not seen using a general untargeted instrument. CONCLUSION: Our observational study found evidence that metformin use reduces the risk of developing AAA. The MR results support this finding, providing evidence that the association may be causal. Clinical trials are warranted to assess the efficacy of metformin to reduce the risk of aneurysm growth and rupture in people with AAA."}